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Azithromycin is a macrolide antibiotic with anti-inflammatory and immunomodulatory properties. We tested the hypothesis that azithromycin would decrease the frequency of exacerbations, increase lung function, and improve health-related quality of life in patients with non-cystic fibrosis bronchiectasis. We undertook a randomised, double-blind, placebo-controlled trial at three centres in New Zealand. Between Feb 12, 2008, and Oct 15, 2009, we enrolled patients who were 18 years or older, had had at least one pulmonary exacerbation requiring antibiotic treatment in the past year, and had a diagnosis of bronchiectasis defined by high-resolution CT scan. We randomly assigned patients to receive 500 mg azithromycin or placebo three times a week for 6 months in a 1:1 ratio, with a permuted block size of six and sequential assignment stratified by centre. Participants, research assistants, and investigators were masked to treatment allocation. The coprimary endpoints were rate of event-based exacerbations in the 6-month treatment period, change in forced expiratory volume in 1 s (FEV1) before bronchodilation, and change in total score on St George's respiratory questionnaire (SGRQ). Analyses were by intention to treat. This study is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12607000641493. 71 patients were in the azithromycin group and 70 in the placebo group. The rate of event-based exacerbations was 0·59 per patient in the azithromycin group and 1·57 per patient in the placebo group in the 6-month treatment period (rate ratio 0·38, 95% CI 0·26–0·54; p<0·0001). Prebronchodilator FEV1 did not change from baseline in the azithromycin group and decreased by 0·04 L in the placebo group, but the difference was not significant (0·04 L, 95% CI −0·03 to 0·12; p=0·251). Additionally, change in SGRQ total score did not differ between the azithromycin (–5·17 units) and placebo groups (–1·92 units; difference −3·25, 95% CI −7·21 to 0·72; p=0·108). Azithromycin is a new option for prevention of exacerbations in patients with non-cystic fibrosis bronchiectasis with a history of at least one exacerbation in the past year. Health Research Council of New Zealand and Auckland District Health Board Charitable Trust.

BackgroundHospitalisation with severe lower respiratory tract infection (LRTI) in early childhood is associated with ongoing respiratory symptoms and possible later development of bronchiectasis. We aimed to reduce this intermediate respiratory morbidity with a community intervention programme at time of discharge.MethodsThis randomised, controlled, single-blind trial enrolled children aged <2 years hospitalised for severe LRTI to ‘intervention’ or ‘control’. Intervention was three monthly community clinics treating wet cough with prolonged antibiotics referring non-responders. All other health issues were addressed, and health resilience behaviours were encouraged, with referrals for housing or smoking concerns. Controls followed the usual pathway of parent-initiated healthcare access. After 24 months, all children were assessed by a paediatrician blinded to randomisation for primary outcomes of wet cough, abnormal examination (crackles or clubbing) or chest X-ray Brasfield score ≤22.Findings400 children (203 intervention, 197 control) were enrolled in 2011–2012; mean age 6.9 months, 230 boys, 87% Maori/Pasifika ethnicity and 83% from the most deprived quintile. Final assessment of 321/400 (80.3%) showed no differences in presence of wet cough (33.9% intervention, 36.5% controls, relative risk (RR) 0.93, 95% CI 0.69 to 1.25), abnormal examination (21.7% intervention, 23.9% controls, RR 0.92, 95% CI 0.61 to 1.38) or Brasfield score ≤22 (32.4% intervention, 37.9% control, RR 0.85, 95% CI 0.63 to 1.17). Twelve (all intervention) were diagnosed with bronchiectasis within this timeframe.InterpretationWe have identified children at high risk of ongoing respiratory disease following hospital admission with severe LRTI in whom this intervention programme did not change outcomes over 2 years.Trial registration numberACTRN12610001095055.

Substantial population morbidity is likely

BackgroundObservational studies have reported the association between tea consumption and the risk of lower respiratory tract infections (LRTIs). However, a consensus has yet to be reached, and whether the observed association is driven by confounding factors or reverse causality remains unclear.MethodA two-sample Mendelian randomization (MR) analysis was conducted to determine whether genetically predicted tea intake is causally associated with the risk of common LRTI subtypes. Genome-wide association study (GWAS) from UK Biobank was used to identify single-nucleotide polymorphisms (SNPs) associated with an extra cup of tea intake each day. The summary statistics for acute bronchitis, acute bronchiolitis, bronchiectasis, pneumonia, and influenza and pneumonia were derived from the FinnGen project.ResultsWe found that genetically predicted an extra daily cup of tea intake was causally associated with the decreased risk of bronchiectasis [odds ratio (OR) = 0.61, 95% confidence interval (CI) = 0.47–0.78, P < 0.001], pneumonia (OR = 0.90, 95% CI = 0.85–0.96, P = 0.002), influenza and pneumonia (OR = 0.91, 95% CI = 0.85–0.97, P = 0.002), but not with acute bronchitis (OR = 0.91, 95% CI = 0.82–1.01, P = 0.067) and acute bronchiolitis (OR = 0.79, 95% CI = 0.60–1.05, P = 0.100). Sensitivity analyses showed that no heterogeneity and pleiotropy could bias the results.ConclusionsOur findings provided new evidence that genetically predicted an extra daily cup of tea intake may causally associated with a decreased risk of bronchiectasis, pneumonia, and influenza and pneumonia.

Background: Persistent bacterial bronchitis (PBB) seems to be under-recognised and often misdiagnosed as asthma. In the absence of published data relating to the management and outcomes in this patient group, a review of the outcomes of patients with PBB attending a paediatric respiratory clinic was undertaken. Methods: A retrospective chart review was undertaken of 81 patients in whom a diagnosis of PBB had been made. Diagnosis was based on the standard criterion of a persistent, wet cough for >1 month that resolves with appropriate antibiotic treatment. Results: The most common reason for referral was a persistent cough or difficult asthma. In most of the patients, symptoms started before the age of 2 years, and had been present for >1 year in 59% of patients. At referral, 59% of patients were receiving asthma treatment and 11% antibiotics. Haemophilus influenzae and Streptococcus pneumoniae were the most commonly isolated organisms. Over half of the patients were completely symptom free after two courses of antibiotics. Only 13% of patients required ⩾6 courses of antibiotics. Conclusion: PBB is often misdiagnosed as asthma, although the two conditions may coexist. In addition to eliminating a persistent cough, treatment may also prevent progression to bronchiectasis. Further research relating to both diagnosis and treatment is urgently required.

BackgroundSeveral pharmacological and non-pharmacological therapies are used to treat stable bronchiectasis of non-cystic fibrosis (CF) aetiology.ObjectiveWe conducted a systematic review and meta-analysis to assess the evidence of the effectiveness of pharmacological and non-pharmacological treatment options in patients with stable non-CF bronchiectasis with a focus on reducing exacerbations.Study selectionMultiple databases were searched through September 2017. Outcomes included the number of patients with exacerbation events, mean number of exacerbations, hospitalisations, mortality, quality of life measures, and safety and adverse effects. Meta-analysis was conducted using the random effects model.Findings30 randomised controlled trials enrolled subjects with non-CF bronchiectasis using different interventions. Moderate-quality evidence supported the effect of long-term antibiotics (≥3 months) on lowering the number of patients experiencing exacerbation events (relative risk 0.77 (95% CI 0.68 to 0.89)), reducing number of exacerbations (incidence rate ratio 0.62 (95% CI 0.49 to 0.78)), improving forced expiratory volume (litre) in the first second (FEV1) (weighted mean difference (WMD); 0.02 (95% CI 0.00 to 0.04)), decreasing sputum purulence scores (numerical scale of 1-8) (WMD −0.90 (95% CI −1.58 to −0.22)) and improving quality of life scores assessed by the St George’s Respiratory Questionnaire (WMD −6.07 (95% CI −10.7 to −1.43)). Bronchospasm increased with inhaled antibiotics while diarrhoea increased particularly with oral macrolide therapy.ConclusionsModerate-quality evidence supports long-term antibiotic therapy for preventing exacerbations in stable non-CF bronchiectasis. However, data about the optimum agent, mode of therapy and length of treatment are limited. There is paucity of high-quality evidence to support the management of stable non-CF bronchiectasis including prevention of exacerbations.

[...]at screening, our rate of positive cultures would be expected to be low, and proved to be lower than the 2% rate described in a study of highly selected patients with bronchiectasis in the UK.2 Our patients also had CT scans before inclusion in the study.

In view of the confounding effect of the normal range of pulmonary function tests and the possibility that the treatment effect does have some relation to disease severity as suggested by the analyses of scores on the St George's Respiratory Questionnaire, Wong and colleagues might usefully have investigated associations between treatment effects and high-resolution CT findings.

Additionally, although Wong and colleagues warn of the risk of macrolide resistance in Streptococcus pneumoniae, we and others have shown that macrolide monotherapy is the most important risk factor for infection with macrolide-resistant Mycobacterium avium complex.5 We wholeheartedly agree with the suggestion to screen candidates for NTM before starting azithromycin monotherapy, but we also recommend that physicians be vigilant in monitoring for symptoms and signs of NTM lung disease and for having a low threshold for repeating sputum microbiology tests for acid-fast bacilli.

The Seminar by Miguel Park and colleagues (Aug 9, p 489) gives an excellent update on emerging knowledge of the heterogeneous antibody deficiency syndrome common variable immunodeficiency. What the paper fails to do, however, is help identify key management issues and illuminate care plans. In three short sentences antibiotic treatment is recommended then dismissed without specific guidance. This shortfall is common and reflects the diverse specialist needs of individuals with common variable immunodeficiency.